CELLULAR METABOLISM AND FERMENTATION

Table of Contents

Nine reactions, each catalyzed by a specific
enzyme, makeup the process we call glycolysis.
ALL organisms have glycolysis occurring in their cytoplasm.

At steps 1 and 3 ATP is converted into ADP,
inputting energy into the reaction as well as attaching a phosphate
to the glucose. At steps 6 and 9 ADP is converted into the higher
energy ATP. At step 5 NAD+ is converted into NADH +
H+.

The process works on glucose, a 6-C, until step 4
splits the 6-C into two 3-C compounds. Glyceraldehyde phosphate (GAP,
also known as phosphoglyceraldehyde, PGAL) is the more readily used
of the two. Dihydroxyacetone phosphate can be converted into GAP by
the enzyme Isomerase. The end of the glycolysis process yields two
pyruvic acid (3-C) molecules, and a net gain of 2 ATP and two NADH
per glucose.

Graphic summary of the glycolysis process.
Image from Purves et al., Life: The Science of Biology, 4th
Edition, by Sinauer Associates (www.sinauer.com)
and WH Freeman (www.whfreeman.com),
used with permission.

Under anaerobic
conditions, the absence of oxygen, pyruvic acid can be routed by the
organism into one of three pathways: lactic acid fermentation,
alcohol fermentation, or cellular (anaerobic) respiration. Humans
cannot ferment alcohol in their own bodies, we lack the genetic
information to do so. These biochemical pathways, with their myriad
reactions catalyzed by reaction-specific enzymes all under genetic
control, are extremely complex. We will only skim the surface at this
time and in this course.

Alcohol fermentation
is the formation of alcohol from sugar. Yeast, when under anaerobic
conditions, convert glucose to pyruvic acid via the glycolysis
pathways, then go one step farther, converting pyruvic acid into
ethanol, a C-2 compound.

Fermentation of ethanol. Image from Purves
et al., Life: The Science of Biology, 4th Edition, by Sinauer
Associates (www.sinauer.com) and
WH Freeman (www.whfreeman.com),
used with permission.

Many organisms will also ferment pyruvic acid
into, other chemicals, such as lactic acid. Humans ferment lactic
acid in muscles where oxygen becomes depleted, resulting in localized
anaerobic conditions. This lactic acid causes the muscle stiffness
couch-potatoes feel after beginning exercise programs. The stiffness
goes away after a few days since the cessation of strenuous activity
allows aerobic conditions to return to the muscle, and the lactic
acid can be converted into ATP via the normal aerobic respiration
pathways.

When oxygen is present (aerobic conditions), most
organisms will undergo two more steps, Kreb's
Cycle, and Electron
Transport, to produce their ATP. In
eukaryotes, these processes occur in the mitochondria, while in
prokaryotes they occur in the cytoplasm.

Overview of the cellular respiration
processes. Image from Purves et al., Life: The Science of
Biology, 4th Edition, by Sinauer Associates (www.sinauer.com)
and WH Freeman (www.whfreeman.com),
used with permission.

Acetyl Co-A: The Transition Reaction

Pyruvic acid is first altered in the
transition
reaction by removal of a carbon and two
oxygens (which form carbon dioxide). When the carbon dioxide is
removed, energy is given off, and NAD+ is converted into the higher
energy form NADH. Coenzyme A attaches to the remaining 2-C (acetyl)
unit, forming acetyl
Co-A. This process is a prelude to the
Kreb's Cycle.

Kreb's Cycle (aka Citric Acid Cycle)

The Acetyl Co-A (2-C) is attached to a 4-C
chemical (oxaloacetic acid). The Co-A is released and returns to
await another pyruvic acid. The 2-C and 4-C make another chemical
known as Citric acid, a 6-C. Kreb's Cycle is also known as the Citric
Acid Cycle. The process after Citric Acid is essentially removing
carbon dioxide, getting out energy in the form of ATP, GTP, NADH and
FADH2, and lastly regenerating the cycle. Between
Isocitric Acid and a-Ketoglutaric
Acid, carbon dioxide is given off and NAD+ is converted into NADH.
Between a-Ketoglutaric
Acid and Succinic Acid the release of carbon dioxide and reduction of
NAD+ into NADH happens again, resulting in a 4-C chemical,
succinic acid. GTP (Guanine Triphosphate, which transfers its energy
to ATP) is also formed here (GTP is formed by attaching a phosphate
to GDP).

The remaining energy carrier-generating steps
involve the shifting of atomic arrangements within the 4-C molecules.
Between Succinic Acid and Fumaric Acid, the molecular shifting
releases not enough energy to make ATP or NADH outright, but instead
this energy is captured by a new energy carrier, Flavin adenine
dinucleotide (FAD). FAD is reduced by the addition of two H's to
become FADH2. FADH2 is not as rich an energy
carrier as NADH, yielding less ATP than the latter.

The last step, between Malic Acid and Oxaloacetic
Acid reforms OA to complete the cycle. Energy is given off and
trapped by the reduction of NAD+ to NADH. The carbon
dioxide released by cells is generated by the Kreb's Cycle, as are
the energy carriers (NADH and FADH2) which play a role in
the next step.

Electron Transport Phosphorylation

Whereas Kreb's Cycle occurs in the matrix of the
mitochondrion, the Electron Transport System (ETS) chemicals are
embedded in the membranes known as the cristae.
Kreb's cycle completely oxidized the carbons in the pyruvic acids,
producing a small amount of ATP, and reducing NAD and FAD into higher
energy forms. In the ETS those higher energy forms are cashed in,
producing ATP. Cytochromes are molecules that pass the "hot potatoes"
(electrons) along the ETS chain. Energy released by the "downhill"
passage of electrons is captured as ATP by ADP molecules. The ADP is
reduced by the gain of electrons. ATP formed in this way is made by
the process of oxidative phosphorylation. The mechanism for the
oxidative phosphorylation process is the gradient of H+
ions discovered across the inner mitochondrial membrane. This
mechanism is known as chemiosmotic
coupling. This involves both chemical and transport processes. Drops
in the potential energy of electrons moving down the ETS chain occur
at three points. These points turn out to be where ADP + P are
converted into ATP. Potential energy is captured by ADP and stored in
the pyrophosphate bond. NADH enters the ETS chain at the beginning,
yielding 3 ATP per NADH. FADH2 enters at Co-Q, producing
only 2 ATP per FADH2.